1146.1: Final
Decision Analytical
Protocol (DAP) to
guide the assessment
of capsule endoscopy
for patients with
suspected small
bowel Crohn’s
disease
July 2013
1
Table of Contents
MSAC and PASC ........................................................................................................................ 3
Purpose of this document ........................................................................................................... 3
Issue on which PASC seeks input ................................................................................................ 3
Purpose of application ................................................................................................................ 4
Background .............................................................................................................................. 4
Current arrangements for public reimbursement........................................................................... 4
Regulatory status ................................................................................................................... 6
Intervention ............................................................................................................................. 7
Description................................................................................................................................. 7
Delivery of the intervention ......................................................................................................... 8
Size of the eligible patient population in Australia ......................................................................... 9
Prerequisites .............................................................................................................................. 9
Co-administered and associated interventions ............................................................................ 10
Listing proposed and options for MSAC consideration ..........................................................10
Proposed MBS listing ................................................................................................................ 10
Clinical place for proposed intervention ...................................................................................... 11
Abdominal CT and CTE ....................................................................................... 12
SBFT
12
MRI and MRE ..................................................................................................... 12
Comparator ............................................................................................................................15
Clinical claim ............................................................................................................................ 15
Outcomes and health care resources affected by introduction of proposed intervention ................ 16
Outcomes ................................................................................................................................ 16
Health care resources ............................................................................................................... 18
Summary of PICO to be used for assessment of evidence (systematic review) ............................. 20
Proposed structure of the decision analytic economic evaluation ................................................. 20
References .............................................................................................................................25
Appendix: Applicant’s response to issues in the prior assessment .......................................26
Issues identified in the prior assessment .................................................................................... 26
Safety
29
2
MSAC and PASC
The Medical Services Advisory Committee (MSAC) is an independent expert committee appointed by
the Australian Government Health Minister to strengthen the role of evidence in health financing
decisions in Australia. MSAC advises the Commonwealth Minister for Health and Ageing on the
evidence relating to the safety, effectiveness, and cost-effectiveness of new and existing medical
technologies and procedures and under what circumstances public funding should be supported.
The Protocol Advisory Sub-Committee (PASC) is a standing sub-committee of MSAC. Its primary
objective is the determination of protocols to guide clinical and economic assessments of medical
interventions proposed for public funding.
Purpose of this document
This document is intended to provide a draft decision analytic protocol (DAP) that will be used to
guide the assessment of capsule endoscopy for patients with suspected small bowel Crohn’s disease.
The draft protocol was prepared by Given Imaging and revised following PASC input. The DAP will be
finalised after inviting relevant stakeholders to provide input to the protocol. The final protocol will
provide the basis for the assessment of the intervention.
The protocol guiding the assessment of the health intervention has been developed using the widely
accepted “PICO” approach. The PICO approach involves a clear articulation of the following aspects of
the research question that the assessment is intended to answer:
Patients – specification of the characteristics of the patients in whom the intervention is to be
considered for use;
Intervention – specification of the proposed intervention
Comparator – specification of the therapy most likely to be replaced by the proposed
intervention
Outcomes – specification of the health outcomes and the healthcare resources likely to be
affected by the introduction of the proposed intervention
PASC considered that the service should be performed within 6 months of the prior colonoscopy and
radiographic imaging.
Issue on which PASC seeks input
The PASC invites comment on the following matters:

Is it appropriate to require that capsule endoscopy is performed within six months of the prior
radiographic imaging?
3
Purpose of application
This application requesting MBS listing of capsule endoscopy for patients with suspected small bowel
Crohn’s disease has been developed by Given Imaging for the Department of Health and Ageing
(DoHA). Capsule endoscopy involves using a small pill-shaped camera to examine parts of the small
intestine that cannot be seen by other types of endoscopy. By detecting mucosal abnormalities in the
small bowel, capsule endoscopy can be used to diagnose patients with small bowel Crohn’s disease
who are unable to be diagnosed with colonoscopy with ileoscopy and small bowel radiology.
Capsule endoscopy will be used to provide an additional diagnostic modality to those currently
available to confirm the diagnosis of Crohn’s disease where there is residual diagnostic doubt. MSAC
concluded that, in this overall context, a clear clinical need remains for confirmatory diagnosis in a
residual small number (estimated at 5%) of patients for whom a clinical suspicion of small bowel
Crohn’s disease cannot be excluded.
Background
Current arrangements for public reimbursement
Capsule endoscopy is currently listed on the MBS to investigate an episode of obscure gastrointestinal
bleeding (OGIB, Item 11820), or to conduct small bowel surveillance of a patient diagnosed with
Peutz-Jeghers syndrome (Item 11823). The current MBS item descriptors for these two indications
are presented in Table 1Error! Reference source not found. and Table 2.
4
Table 1 Current MBS item descriptor for Item 11820
Category 2 – Diagnostic procedures and investigations
MBS 11820
CAPSULE ENDOSCOPY to investigate an episode of obscure gastrointestinal bleeding, using a capsule endoscopy
device approved by the Therapeutic Goods Administration (including administration of the capsule, imaging, image reading
and interpretation, and all attendances for providing the service on the day the capsule is administered), (not being a
service associated with double balloon enteroscopy), if:
(a) the service is performed by a specialist or consultant physician with endoscopic training that is recognised by The
Conjoint Committee for the Recognition of Training in Gastrointestinal Endoscopy; and
(b) the patient to whom the service is provided:
(i) is aged 10 years or over; and
(ii) has recurrent or persistent bleeding; and
(iii) is anaemic or has active bleeding; and
(c) an upper gastrointestinal endoscopy and a colonoscopy have been performed on the patient and have not identified the
cause of the bleeding; and
(d) the service is performed within 6 months of the upper gastrointestinal endoscopy and colonoscopy
(e) the service is not associated with double balloon enteroscopy
(f) the service has not been provided to the same patient:
(i) more than once in an episode of bleeding, being bleeding occurring within 6 months of the prerequisite upper
gastrointestinal endoscopy and colonoscopy (any bleeding after that time is considered to be a new episode); or
(ii) on more than 2 occasions in any 12 month period.
Fee: $2,039.20 Benefit: 75% = $1,529.40 85% = $1,964.70
Capsule endoscopy is primarily used to view the small bowel, which cannot be viewed by upper gastrointestinal endoscopy
and colonoscopy.
Conjoint committee
The Conjoint Committee comprises representatives from the Gastroenterological Society of Australia (GESA), the Royal
Australasian College of Physicians (RACP) and the Royal Australasian College of Surgeons (RACS). For the purposes of
Item 11820, specialists or consultant physicians performing this procedure must have endoscopic training recognised by
The Conjoint Committee for the Recognition of Training in Gastrointestinal Endoscopy, and Medicare Australia notified of
that recognition.
5
Table 2: Current MBS item descriptor for Item 11823
Category 2 – Diagnostic procedures and investigations
MBS 11823
CAPSULE ENDOSCOPY to conduct small bowel surveillance of a patient diagnosed with Peutz-Jeghers syndrome, using
a capsule endoscopy device approved by the Therapeutic Goods Administration. The procedure includes the
administration of the capsule, imaging, image reading and interpretation, and all attendances for providing the service on
the day the capsule is administered (not being a service associated with double balloon enteroscopy).
Medicare benefits are only payable for this item if:
1. the service has been performed by a specialist or consultant physician with endoscopic training that is recognised by the
Conjoint Committee for the Recognition of Training in Gastrointestinal Endoscopy; and
2. the patient to whom the service is provided has been conclusively diagnosed with Peutz-Jeghers syndrome (PJS)
This item is available once in any two year period.
Fee: $2,039.20 Benefit: 75% = $1,529.40 85% = $1,964.70
Conjoint committee
The Conjoint Committee comprises representatives from the Gastroenterological Society of Australia (GESA), the Royal
Australasian College of Physicians (RACP) and the Royal Australasian College of Surgeons (RACS). For the purposes of
Item 11823, specialists or consultant physicians performing this procedure must have endoscopic training recognised by
The Conjoint Committee for the Recognition of Training in Gastrointestinal Endoscopy, and Medicare Australia notified of
that recognition.
The utilisation of capsule endoscopy for these indications from 1 June 2003 to 31 July 2012 is
presented in Table 3. Capsule endoscopy was first listed for interim funding in 2003 for the treatment
of OGIB. The indication was extended to include Peutz-Jehgers syndrome in 2008. Between 1 June
2011 and 31 July 2012, a total of 8,989 services were claimed for both indications.
Table 3 Utilisation of MBS items 11820 and 11823 between 2007 and 2012 (financial year 1 June -31 July)
Item
200320042005200620072008200920102011number
2004
2005
2006
2007
2008
2009
2010
2011
2012
11820
134
2,556
3,613
4,957
6,240
7,341
8,165
8,485
8,950
11823
0
0
0
0
0
3
31
27
39
Total
134
2,556
3,613
4,957
6,240
7,344
8,196
8,512
8,989
Source: https://www.medicareaustralia.gov.au/
Capsule endoscopy is currently not funded through Medicare for the diagnosis of suspected small
bowel Crohn’s disease. Patients who wish to use capsule endoscopy to diagnose small bowel Crohn’s
disease after having failed other diagnostic techniques must pay for the procedure out of their own
pockets. In a small number of cases, the procedure may also be paid for by public hospitals.
In the Public Summary Document for the previous application, MSAC noted that a proportion of
patients with undiagnosed Crohn’s disease may present with OGIB and would currently undergo
capsule endoscopy under MBS item 11820 (MSAC 2011, pg. 8).
Regulatory status
PillCam® SB capsules (Given Imaging) have been registered by the TGA since August 2006 (see Table
4). There are no specific conditions on its TGA certification.
6
Table 4 Registration of PillCam® SB capsule endoscopy with the TGA
ARTG no
Product no
Product description
Device class
Sponsor
130833
215817
Given diagnostic
system and
PillCam® SB capsule
endoscopy
(capsule, nondigestible, electronic
tracking)
Class IIa
Given Imaging Pty Ltd
Source: TGA (2013)
Other brands of capsule endoscopes that are TGA-listed are:

MiRo-Cam (Intromedic)

EndoCapsule (Olympus)

CapsoVision (CapsoVision Inc.)
The PASC determined that the assessment of capsule endoscopy should include all capsule
endoscope devices currently registered by the TGA. The item descriptor for the requested indication
should not specify a particular brand of device.
Intervention
Description
Capsule endoscopy is a minimally invasive diagnostic test, conducted in an outpatient setting, in
which the gastrointestinal system is visualised via a camera inside an ingested capsule. As the capsule
passes through the digestive system, it transmits multiple digital images of the small bowel to sensors
on a belt attached to the patient’s abdomen. The test visualises the gastrointestinal tract mucosa to
diagnose a range of conditions such as OGIB, coeliac disease and small bowel tumours.
The current application requests an extension to the current MBS listing for capsule endoscopy to also
include the diagnosis of suspected small bowel Crohn’s disease. Crohn’s disease is a chronic
inflammatory bowel disease that may affect any portion of the gastrointestinal tract but, in cases of
small bowel involvement, typically affects the terminal ileum (Yamada et al., 2009). Crohn's disease is
believed to be caused by interactions between environmental, immunological and bacterial factors in
genetically susceptible individuals. These factors result in a chronic inflammatory disorder, in which
the body's immune system attacks the gastrointestinal tract possibly directed at microbial antigens. It
primarily causes abdominal pain, diarrhoea, vomiting, or weight loss, but may also cause local
complications (e.g., bleeding, obstruction, fistulae) and complications outside the gastrointestinal
tract (e.g., skin rashes, arthritis, inflammation of the eye and fatigue).
The primary goal in treating Crohn's disease is to reduce the underlying inflammation, which then
relieves symptoms, prevents complications, and corrects nutritional deficiencies. Medications used in
reducing
inflammation in Crohn's disease
include
anti-inflammatory drugs, corticosteroids,
immunosuppressants, biologic agents such as TNF-alpha inhibitors, and antibiotics. If drugs are not
7
successful in suppressing inflammation, the alternative is surgery to remove the diseased part of the
intestine.
Most patients with isolated small bowel Crohn’s disease are diagnosed using colonoscopy with
ileoscopy; however diagnosis can be difficult due to the inaccessibility of the small bowel. Capsule
endoscopy is able to visualise areas of the small bowel inaccessible to upper and lower endoscopy.
Capsule endoscopy will be positioned after small bowel follow through (SBFT) or computed
tomography (CT) with or without enterography or magnetic resonance imaging (MRI) with or without
enterography. Capsule endoscopy will provide an additional testing modality prior to treatment, based
on a suspicion of small bowel Crohn’s disease which could not be confirmed through prior testing.
Other techniques used in the diagnosis of Crohn’s disease, such as balloon enteroscopy and push
enteroscopy, are not widely used and not currently funded by Medicare for the investigation of
suspected small bowel Crohn’s disease. Therefore, capsule endoscopy should be essentially regarded
as a last-line approach to diagnosis, for use in patients who cannot be diagnosed through using other
tests. The procedure will be restricted to patients with suspected but unconfirmed small bowel
Crohn’s disease, as indicated by ongoing symptoms suggestive of Crohn’s disease such as abdominal
pain, diarrhoea, extraintestinal symptoms or raised inflammatory markers on blood tests.
The PASC determined that patients with known strictures previously identified through small bowel
imaging (SBFT, CT or MRI) will not be eligible to undergo capsule endoscopy.
Delivery of the intervention
Capsule endoscopy relies on three pieces of equipment – a video capsule, a data recorder and a
workstation. The capsule is disposable and ingestible and contains micro-imaging video technology
which includes a battery, camera, transmitter, antenna and light emitting diodes (Sidhu et al., 2008).
The data recorder is a system worn at the waist that receives the transmitted images via
radiofrequency data transmission. The workstation is a dedicated computer station to which data and
images are uploaded for analysis by the clinician.
The procedure may be performed in an outpatient setting. After bowel preparation, where necessary,
and fasting for 8 to 12 hours, the patient presents at the specialist’s private room (or clinic) to have
the data recorder fitted and to swallow the capsule endoscope with a glass of water (Sidhu et al.,
2008). Images and data are acquired as the capsule endoscope passes through the digestive system
over an 8-hour period. This information is transmitted to the portable recorder attached to a belt
worn around the patient's waist. Once the patient swallows the capsule, they can continue with their
daily activities. After eight hours, they return to the physician’s office with the recorder so the images
can be downloaded and reviewed by the physician. The disposable capsule will usually be excreted
naturally between 24 and 72 hours after ingestion.
The PASC considered that technical failure rates were likely to be low but that a technical failure
would result in a second Medicare claim for a repeat capsule endoscopy procedure. Repeat
procedures due to technical failure should be included in the economic evaluation.
If the capsule endoscope is unable to adequately visualise the small bowel for reasons other than
technical failure, this would be identified in studies of diagnostic accuracy and will also be accounted
for in the economic evaluation. Once a successful reading has been made, it is not expected that
8
capsule endoscopy would be used again in relation to suspected small bowel Crohn’s disease. It is
proposed that the number of capsule endoscopies allowed for each patient should be limited to a
maximum of two per year, to allow for repeat procedures due to technical or other failures.
Patients with Crohn’s disease typically have a higher frequency of strictures than other forms of
inflammatory bowel disease. The presence of strictures can be identified through prior small bowel
imaging with SBFT, CT and/or MRI, which, according to the requested MBS restriction, are
prerequisites for access to capsule endoscopy in patients with suspected Crohn’s disease. The
sensitivity of CT enteroscopy (CTE) and MRI enteroscopy (MRE) in identifying strictures is wellestablished (Vogel et al., 2007).
Consistent with other MBS listings of capsule endoscopy, it is presumed that capsule endoscopy
services will only be reimbursed for public funding when performed by a specialist or consultant
physician with endoscopic training recognised by The Conjoint Committee for the Recognition of
Training in Gastrointestinal Endoscopy (and Medicare Australia is notified of that recognition).
Size of the eligible patient population in Australia
So far there is a lack of prevalence data on Crohn’s disease in Australia. According to the ABS
National Health Survey (NHS) 2004-05, which is based on self-reported data, there were 51,900
people (18,600 males and 33,400 females) with Crohn’s disease and ulcerative colitis in Australia in
that year. This was equivalent to a prevalence rate of 0.26%. An Access Economics report on the
economic costs of Crohn’s disease and ulcerative colitis (Access Economics, 2007) combined these
data with other sources to estimate that there were 28,000 Australians with Crohn’s disease in 2005.
As capsule endoscopy will be used in patients with suspected Crohn’s disease (i.e. those who have
not been diagnosed yet), the prevalence rate is not as important for estimating utilisation as the
incidence rate.
Incidence data for Crohn’s disease are also scarce; however, one Australian study in the regional
Victorian city of Geelong found a crude annual incidence of 17.4 (95% CI =13 to 23) per 100,000 in
2008 (Wilson et al 2010). Using Australian Bureau of Statistics (ABS) population projections, it is
expected that the incidence of Crohn’s disease in 2013 will be 3,998 patients. Approximately 70%
(2,799) of cases will be diagnosed using endoscopy, as there is no small intestine involvement.
Because of some of the symptomatic similarities between Crohn’s disease and OGIB, a number
(approximately 11%) of patients with suspected Crohn’s disease will have previously undergone
capsule endoscopy using the MBS listing for suspected OGIB. Of those patients who weren’t
diagnosed through endoscopy (including capsule endoscopy for OGIB), it is estimated that up to 82%
could be subsequently diagnosed using CT or CTE (Solem et al., 2008). Once these cases are
subtracted from the original incidence of Crohn’s disease, there remain approximately 160
unconfirmed true cases of the condition.
Prerequisites
According to the proposed MBS item descriptor, patients eligible to receive capsule endoscopy will
have undergone prior endoscopy, including colonoscopy with ileoscopy, and prior radiographic
imaging with SBFT, CT/CTE or MRI/MRE.
9
Capsule endoscopy is already used in Australia, and is currently listed on the MBS to investigate an
episode of OGIB (Item 11820), or to conduct small bowel surveillance of a patient diagnosed with
Peutz-Jeghers syndrome (Item 11823). If the requested indication is also funded, the technology will
continue to be used by the same providers who already have the minimal infrastructure in place.
Co-administered and associated interventions
Capsule endoscopy does not involve or require co-dependent assessment by MSAC or the PBAC. The
therapies used by patients diagnosed with Crohn’s disease will not change if capsule endoscopy is
reimbursed. The clinical claim presented in the current DAP is that by using capsule endoscopy, the
proportion of patients who are incorrectly treated (usually with salicylates [e.g., 5-aminosalicylic acid,
5-ASA] or corticosteroids) will decrease.
Listing proposed and options for MSAC consideration
Proposed MBS listing
The proposed MBS item descriptor is presented in Table 5 below.
The PASC determined that the proposed service would be limited to patients aged 2 years and over,
consistent with the current TGA listing.
The procedure will be restricted to patients aged 2 years and over with suspected but unconfirmed
small bowel Crohn’s disease, as indicated by ongoing symptoms suggestive of Crohn’s disease such
as abdominal pain, diarrhoea, extraintestinal symptoms and raised inflammatory markers on blood
tests. Patients who are eligible for capsule endoscopy will have undergone prior endoscopy or
radiographic imaging and not have received a confirmed positive or negative diagnosis for Crohn’s
disease or evidence of strictures.
The PASC considered that patients with suspected strictures on prior imaging would be excluded.
Consequently, the PASC determined that the use of a patency capsule was outside the scope of the
current DAP.
Radiographic imaging may include magnetic resonance imaging with or without enterography
(MRI/MRE), computed tomography with or without enterography (CT/CTE) or SBFT. It should be
noted that CT/CTE and SBFT are currently reimbursed through Medicare for the diagnosis of Crohn’s
disease, while an application to MSAC for the use of MRI/MRE in the same indication is currently
being assessed (MSAC Application 1190).
The PASC considered that the service should be performed within 6 months of the prior colonoscopy
and radiographic imaging. The PASC also determined that the item descriptor should limit the number
of services to 2 in any 12 month period.
The wording around the requirement that capsule endoscopy be administered by a specialist or
consultant physician with endoscopic training that is recognised by the Conjoint Committee is adapted
from the existing item descriptors for capsule endoscopy in the diagnosis of OGIB and Peutz-Jeghers
Syndrome.
10
Table 5: Proposed MBS item descriptor
Category 2 – Diagnostic procedures and investigations
MBS TBD
CAPSULE ENDOSCOPY to diagnose suspected small bowel Crohn’s disease, using a capsule endoscopy device
approved by the Therapeutic Goods Administration (including administration of the capsule, imaging, image reading and
interpretation, and all attendances for providing the service on the day the capsule is administered), if:
(a) the patient to whom the service is provided:
(i) is aged 2 years or over; and
(ii) has not previously been diagnosed with Crohn’s disease; and
(ii) has suspected small bowel Crohn’s disease on the basis of clinical findings and evidence of underlying
inflammation, as indicated by elevated Erythrocyte Sedimentation Rate and/or C-Reactive Protein or other
inflammatory markers; and
(b) the service is performed by a specialist or consultant physician with endoscopic training that is recognised by The
Conjoint Committee for the Recognition of Training in Gastrointestinal Endoscopy; and
(c) prior negative endoscopy including colonoscopy with ileoscopy has been performed on the patient, and has not
produced a confirmed positive or negative diagnosis of Crohn’s disease; and
(d) prior radiographic imaging has been performed on the patient, and has not produced a confirmed positive or negative
diagnosis of Crohn’s disease or evidence of strictures. Radiographic diagnostic procedures previously used by the patient
may include:
(i) computed tomography with or without enterography (CT or CTE), or
(ii) small bowel follow through (SBFT) testing; or
(iii) magnetic resonance imaging with or without enterography (MRI or MRE); and
(e) the service is performed within 6 months of the colonoscopy and radiographic imaging; and
(f) the service is not associated with balloon enteroscopy; and
(g) the service has not been provided to the same patient on more than 2 occasions in any 12 month period.
Fee: $2,039.20 Benefit: 75% = $1,529.40 85% = $1,964.70
Conjoint committee
The Conjoint Committee comprises representatives from the Gastroenterological Society of Australia (GESA), the Royal
Australasian College of Physicians (RACP) and the Royal Australasian College of Surgeons (RACS). For the purposes of
Item TBD, specialists or consultant physicians performing this procedure must have endoscopic training recognised by The
Conjoint Committee for the Recognition of Training in Gastrointestinal Endoscopy, and Medicare Australia notified of that
recognition.
Clinical place for proposed intervention
Precise diagnosis is essential for the effective treatment of Crohn’s disease; however, achieving a
definitive diagnosis can be difficult, partly because of the inaccessibility of the small bowel. Therefore,
the diagnostic algorithm for Crohn’s disease is based on a composite of endoscopic, radiographic, and
pathological findings.
Optimal health outcomes are achieved through accurately identifying positive cases of Crohn’s
disease, and excluding patients without Crohn’s disease as early as possible in the diagnostic
pathway. A suspicion of Crohn’s disease is usually established on the basis of history, physical
examination and the results of blood tests for inflammatory markers, anaemia and infection. Initial
assessment usually involves endoscopy, which is reported to be effective in diagnosing approximately
70% of cases (usually those without small intestine involvement). Upper or lower GI endoscopy is
used to confirm the diagnosis of Crohn’s disease, assess disease location, or obtain tissue for
11
pathological evaluation. Endoscopy can also serve a therapeutic role in the dilation of strictures,
particularly those at a surgical anastomosis (Lichtenstien et al., 2009).
If these procedures are unable to achieve a diagnosis, radiologic imaging including MRI, CT or SBFT
testing may be used. The effectiveness of these tests is an important determinant of the prevalence
of Crohn’s disease in patients eligible for investigation with capsule endoscopy. Therefore, the impact
of prior testing and applicability of included studies should be considered in an assessment of the
safety, effectiveness, cost-effectiveness of capsule endoscopy. A description of each of these
radiologic techniques is provided below.
Abdominal CT and CTE
Abdominal CT is a radiological technique used in the diagnosis of small bowel Crohn’s disease. This
test provides multiplanar images of the lumen, wall and mesentery of the small bowel. These images
have a high degree of spatial resolution and are generated via the use of multidetector CT technology
following the ingestion of a contrast agent by the patient, either orally (enterography) or via a nasogastric tube (enteroclysis) (Fletcher et al., 2009). In some Australian settings, CTE has superseded
barium imaging as the main form of radiological imaging used in the diagnosis of Crohn’s disease
Abdomen CT is funded under MBS item 56507 with a fee of $480.05.
SBFT
SBFT is a radiological technique for imaging the small bowel. Barium is either ingested by the patient
or administered via enteroclysis and then x-ray images are taken of the abdomen. In recent years,
MR and CT enterography have overtaken SBFT the most commonly used tools for imaging the small
bowel in suspected Crohn’s disease (Morrison et al., 2009).
SBFT is funded under MBS item 58915 with a fee of $78.95.
MRI and MRE
MRI is an imaging technique that enables cross-sectional imaging of the small bowel (Yamada 2009).
Contrast agents can be administered orally (MRE) or through a nasogastric tube (magnetic resonance
enteroclysis) (Markova et al 2010). Compared with CT, which uses x-ray attenuation, MRI uses
multiple tissue parameters to build an image but, unlike CT and SBFT, does not use ionising
radiation.
MRI is not currently funded through the MBS for small bowel Crohn’s disease.
A DAP to guide the assessment of MRI for small bowel Crohn’s disease has been prepared (MSAC ID
1190).
The current and proposed diagnostic algorithms for Crohn’s disease are presented in Figure 1. Under
the current scenario, if a patient still has unconfirmed disease after going through endoscopic and
radiographic testing, the only option currently available to patients is presumptive treatment. Note
that prior investigations such as colonoscopy, SBFT, CT and MRI are able to make a diagnosis of
Crohn's disease in the majority of patients but not in all because of their inability to examine the small
bowel mucosa directly. This means that they cannot definitely exclude Crohn's disease if no
abnormality is found.
12
Patients in whom there is a high clinical suspicion of Crohn’s disease but who have received
inconclusive results from prior endoscopy and radiography are treated under the assumption that
they have Crohn’s disease, and diagnosis is achieved via response to treatment. In most cases, firstline treatment for small bowel Crohn’s disease involves the use of anti-inflammatory agents such as
5-ASA. If patients do not achieve remission with anti-inflammatory drugs, corticosteroids such as oral
prednisolone may also relieve symptoms. Maintenance therapy consists of continued use of salicylates
or immune-modulators such as azathioprine, 6-mercaptopurine or methotrexate. Patients who fail all
of these therapies may be treated with biological agents such as infliximab or adalimumab (Morrison
et al., 2009).
Treatment may identify patients with Crohn’s disease that are responsive to first-line therapies;
however it also carries the risk of unnecessarily exposing non-Crohn’s patients to therapies with
potentially severe side effects. The benefit associated with treatment is lower in populations with a
lower prevalence of Crohn’s disease, such as those covered by the current DAP, who have already
undergone a range of prior tests.
13
Figure 1 Current and proposed diagnostic algorithms for patients with suspected small bowel Crohn’s disease
14
Comparator
The PASC noted that capsule endoscopy will not replace treatment. Capsule endoscopy will be used
as an additional test prior to treatment. Consequently, the PASC determined that the appropriate
comparator for capsule endoscopy is ‘no capsule endoscopy’.
Consistent with the current and proposed treatment algorithms presented in Figure 1, the comparator
for capsule endoscopy in the diagnosis of suspected Crohn’s disease is ’no capsule endoscopy’. The
approach to the submission is therefore a cost-effectiveness analysis of capsule endoscopy compared
to current clinical practice.
To be eligible for reimbursement, patients with suspected Crohn’s disease will have to first undergo
endoscopy and at least one form of radiographic imaging, including CT, MRI or SBFT and have no
evidence of strictures. In the PSD for the previous MSAC application, MSAC noted the existence of
other diagnostic options such as balloon endoscopy (BE) and push endoscopy, but agreed that from a
consumer’s perspective, capsule endoscopy would be preferable on the grounds of comfort and risk.
As BE and push endoscopy are not currently funded for the investigation of Crohn’s disease and are
not widely used, they are not considered to be appropriate comparators for capsule endoscopy.
Clinical claim
The PASC determined that the main clinical claim in the current DAP is that capsule endoscopy will
identify a subgroup of the tested patients for whom a diagnosis of Crohn’s disease is excluded. These
patients will then avoid inappropriate treatment for Crohn’s disease. A key risk associated with this
use of capsule endoscopy is that patients may receive a false negative test result and will not receive
the required treatment.
While prior tests such as colonoscopy, CT, MRI and SBFT cannot necessarily exclude Crohn’s disease,
capsule endoscopy can provide definitive diagnoses in patients with and without Crohn’s disease (i.e.
fewer patients with an uncertain diagnosis). As a result patients without Crohn’s disease may be
spared the unnecessary harms associated with treatment.
Therefore, the approach taken in the economic evaluation will be a cost-utility analysis, showing that
capsule endoscopy is cost-effective compared to no capsule endoscopy in the requested indication.
Table 6 shows that cost-utility analysis will be the appropriate form of economic evaluation provided
that the assessment can establish the superior effectiveness and superior safety of capsule
endoscopy.
15
Comparative safety
versus comparator
Table 6: Classification of an intervention for determination of economic evaluation to be presented
Comparative effectiveness versus comparator
Superior
Non-inferior
Inferior
Net clinical benefit CEA/CUA
Superior
CEA/CUA
CEA/CUA
Neutral benefit
CEA/CUA*
Net harms
None^
Non-inferior
CEA/CUA
CEA/CUA*
None^
Net clinical benefit
CEA/CUA
Neutral benefit
CEA/CUA*
None^
None^
Net harms
None^
Abbreviations: CEA = cost-effectiveness analysis; CUA = cost-utility analysis
* May be reduced to cost-minimisation analysis. Cost-minimisation analysis should only be presented when the proposed
service has been indisputably demonstrated to be no worse than its main comparator(s) in terms of both effectiveness
and safety, so the difference between the service and the appropriate comparator can be reduced to a comparison of
costs. In most cases, there will be some uncertainty around such a conclusion (i.e., the conclusion is often not
indisputable). Therefore, when an assessment concludes that an intervention was no worse than a comparator, an
assessment of the uncertainty around this conclusion should be provided by presentation of cost-effectiveness and/or
cost-utility analyses.
^ No economic evaluation needs to be presented; MSAC is unlikely to recommend government subsidy of this intervention
Inferior
Outcomes and health care resources affected by introduction of
proposed intervention
The health outcomes upon which the comparative clinical performance of ‘capsule endoscopy’ testing
versus ‘no capsule endoscopy’ will be measured are based on the impact of testing on treatment
decisions and treatment effectiveness. The assessment will present clinical evidence demonstrating
that additional health outcomes of capsule endoscopy are generated by additional diagnostic value
offered by capsule endoscopy, improving the effectiveness of downstream disease management via
improvement in the selection of treatment strategies. That is, in the comparator arm with no capsule
endoscopy, all patients presenting with suspected Crohn’s disease at baseline would receive
treatment for Crohn’s disease based on the findings from the previous tests (i.e., CT, MRI, and SBFT).
With capsule endoscopy, fewer patients would receive inappropriate treatment for Crohn’s disease,
thereby improving health outcomes.
The literature review should focus on studies in which the patient population is applicable to the
requested listing and consistent with the proposed positioning of capsule endoscopy.
Outcomes
The assessment will present evidence to show that capsule endoscopy leads to improved clinical
outcomes in patients with suspected but unconfirmed Crohn’s disease, and who could not be
diagnosed with prior endoscopy and small bowel imaging, including CT, MRI or SBFT. As noted
above, additional health outcomes generated by capsule endoscopy reflect the additional diagnostic
value offered by capsule endoscopy, thereby improving the effectiveness of downstream disease
management via improvement in the treatment strategy.
The literature review will initially search for direct evidence for the impact of capsule endoscopy on
health outcomes; however, based on the results of the previous MSAC Assessment Report for capsule
16
endoscopy in suspected Crohn’s disease, it is unlikely that direct evidence will be available. In this
case, the assessment may present indirect evidence for the impact of capsule endoscopy on clinical
management and patient outcomes i.e. a linked evidence approach. The use of a linked evidence
approach is not unusual when looking at the impact of a diagnostic test on clinical outcomes. Studies
that might be used in a linked evidence approach include the following:
1. Diagnostic accuracy and diagnostic yield studies of capsule endoscopy in the appropriate
population.
2. Studies demonstrating that a capsule endoscopy result leads to a change in patient
management.
3. Studies reporting health outcomes and costs in treated/untreated patients with Crohn’s
disease, a non-Crohn’s condition, and patients with an unconfirmed diagnosis.
Where relevant, these studies will provide comparative data with no testing; however, if needed, the
search will also include non-comparative studies, or studies including comparisons with other
diagnostic modalities.
Specific outcomes that will be searched for in these studies include:

Diagnostic performance (negative predictive value, positive predictive value, sensitivity,
specificity, additional true/false positives, ROC, AUC, Q*, DOR)

Diagnostic yield

Impact on patient management

Patient outcomes (Crohn’s disease treatment outcomes, Crohn’s disease morbidity, quality of
life)

Safety (retention, adverse events (AEs) associated with capsule endoscopy, treatment-related
AEs)
The PASC noted that the risk of capsule retention was low, as patients with small bowel strictures will
have been excluded based on prior imaging. If capsule retention occurs, the capsule would be
removed surgically or by balloon enteroscopy.
While the literature review will include any studies reporting the aforementioned outcomes, it should
be noted that some outcomes may not be identified.
The main clinical claim in the current DAP is that capsule endoscopy will identify a subgroup of the
tested patients for whom a diagnosis of Crohn’s disease is excluded. These patients will then avoid
inappropriate treatment for Crohn’s disease. For this claim, the negative predictive value of capsule
endoscopy is the key measure of diagnostic performance, as patients who test negative for Crohn’s
disease using capsule endoscopy will not receive treatment.
17
As noted previously, prior investigations such as colonoscopy, SBFT, CT and MRI are able to make a
diagnosis of Crohn's disease in the majority of patients but not in all because of their inability to
examine the small bowel mucosa directly. This means that they cannot definitely exclude Crohn's
disease if no abnormality is found. It is therefore expected that the population eligible for
investigation using capsule endoscopy will include a lower prevalence of patients with Crohn’s disease
than the general population of patients with suspected Crohn’s disease. The value of capsule
endoscopy will therefore be its ability to exclude the diagnosis in patients without Crohn’s disease,
and spare them from unnecessary treatment. Therefore, the health outcomes of patients without
Crohn’s disease are the key outcomes of interest in this assessment.
If the review of clinical evidence demonstrates improved health outcomes as a result of the use of
capsule endoscopy, cost-effectiveness and cost-utility analyses would be relevant, and health
outcomes would need to be measured as life-years gained and quality-adjusted life-years gained. The
relevant patient outcomes are expected to include Crohn’s disease progression, treatment selection,
morbidity and quality of life.
Health care resources
The use of capsule endoscopy will not alter the treatment of Crohn’s disease or any of the diagnostic
modalities that precede it in the clinical management pathway. It will, however, alter the proportion
and/or timing at which patients receive treatment for Crohn’s disease and other conditions. The effect
of the introduction of capsule endoscopy on resource use, including hospitalisations and the
management of side effects, will also be considered. The proposal therefore includes the costs for the
following health care resource items

Costs for capsule endoscopy

Costs of retention and other AEs in patients receiving capsule endoscopy

Costs associated with treatment of patients with suspected Crohn’s disease

Costs associated with the management of Crohn’s disease and other bowel diseases

Costs associated with the management of AEs in patients receiving treatment for Crohn’s
disease or other bowel diseases
A non-exhaustive list of the resources that would need to be considered in the economic analysis is
provided in Table 7. The current MBS item fee for capsule endoscopy (based on MBS item numbers
11820 and 11823) is $2,039.20. The listed 85% reimbursement fee for capsule endoscopy is
$1964.70. Consequently, the benefit amount and not the full MBS fee will be used in the cost
calculations, as using the full fee would double count some of the copayment contribution. According
to the 2011 MSAC Assessment report for capsule endoscopy, the average copayment for capsule
endoscopy performed in an outpatient setting is $32.95, which is the average aggregated copayment
for MBS items 11820 and 11823 based on their respective number of services.
18
Table 7 List of resources to be considered in the economic analysis
Provider of
resource
Resources provided to deliver capsule endoscopy
Given
- Capsule endoscopy
Cost of capsule retention
- 1936X Prednisolone
- 30682 Double balloon enteroscopy (DBE)
- G44C Day hospital facilities (DBE)
- G05B Surgery (bowel resection)
Treatment of patients with confirmed diagnosis of Crohn’s disease
- 1936X Prednisolone, 2687K Azathioprine,
9206M Mesalazine
- 13918 Administration cost – IV infusion
- 110/116 Consultant physician, referred
consultation
- AAC27 Casualty visits
- G05B Hospitalisation
- 23 General Practitioner
- 66512 Blood tests: LFT, U&E, CRP
Treatment of patients with suspected diagnosis of Crohn’s disease
- 1936X Prednisolone, 2687K Azathioprine,
9206M Mesalazine
- 13918 Administration cost – IV infusion
- 110/116 Consultant physician, referred
consultation
- AAC27 Casualty visits
- G05B Hospitalisation
- 23 General Practitioner
- 66512 Blood tests: LFT, U&E, CRP
- 56507 Abdomen CT
- 58915 Small bowel follow through
Treatment of patients with alternative diagnoses of Crohn’s disease
- 110/116 Consultant physician
- AAC27 Casualty visits
- G05B Hospitalisation
Setting in
which
resource is
provided
Outpatient
Proportion of
Number of units of
patients
resource per relevant time
receiving
horizon per patient
resource
receiving resource
100%
1
MBS
Safety
nets*
Disaggregated unit cost
Private
Other govt
health
budget
insurer
Patient
Total cost
$2,039.20
The costs of capsule retention will be
presented in detail in the re-submission.
The use of treatments for Crohn’s disease will
be presented in detail in the re-submission.
The use of treatments for alternative
diagnoses will be presented in detail in the resubmission.
$480.05
$78.95
The use of resources to manage the side
effects of treatment in patients with alternative
diagnoses will be presented in detail in the resubmission.
* Include costs relating to both the standard and extended safety net.
Abbreviations: LFT, liver function test; U&E, urea, electrolytes, creatinine; CRP, C-reactive protein
19
Summary of PICO to be used for assessment of evidence
(systematic review)
The key research question in the re-submission is:
“In symptomatic patients with suspected but unconfirmed Crohn’s disease following colonoscopy and
small bowel radiological investigations, what is the value of capsule endoscopy compared with no
capsule endoscopy for the diagnosis of suspected small bowel Crohn’s disease?”
The complete details of the research question can be found in the PPICO criteria presented in Table
8.
Consistent with the requested MBS listing, the population of interest is patients with suspected
Crohn’s disease. All patients must have attempted diagnosis with prior endoscopy (including
colonoscopy with ileoscopy) and small bowel imaging including CT, MRI or SBFT. Under the proposed
diagnostic algorithm capsule endoscopy will provide an additional testing modality prior to treatment
(see Figure 1).
The PASC agreed that the appropriate reference standard for the clinical response to treatment is 12
months of follow-up.
The literature review presented in the re-submission will be based on the PPICO criteria described in
Table 8.
Table 8 Summary of PPICO to define research questions for capsule endoscopy testing
Patients
Patients aged 2 years
or over with suspected
but unconfirmed small
bowel Crohn’s disease
on the basis of evidence
of underlying
inflammation, as
indicated by elevated
Erythrocyte
Sedimentation Rate
and/or C-Reactive
Protein or other
inflammatory markers
Prior Tests
Endoscopy including
colonoscopy with
ileoscopy; AND
Radiographic imaging
including:
i.
MRI, or
ii.
CT, or
iii.
SBFT
Intervention
Capsule
endoscopy
Comparator
No capsule
endoscopy
Outcomes to be
assessed
Reference Standard
Diagnosis at 12 months
Diagnostic
performance
Negative predictive
value; Positive
predictive value,
Sensitivity, Specificity
ROC, AUC, Q*, DOR
Diagnostic yield
Impact on patient
management
Patient outcomes
Crohn’s disease
treatment outcomes
Crohn’s disease
morbidity Quality of life
Safety
Retention
AEs
Healthcare
resources to be
considered
See Table 7
Proposed structure of the decision analytic economic evaluation
The following section describes a proposed modelling strategy which is subject to change based on
the available clinical evidence. However, the fundamental approach would most likely remain
20
unchanged; that is, capsule endoscopy provides additional diagnostic value provides better targeted
treatment selection, providing additional health outcomes.
The structure of the economic evaluation will align with the linked evidence approach described
earlier. That is, capsule endoscopy affects the proportion of patients who receive a confirmed
diagnosis (i.e., diagnostic yield; while some of them may be false diagnoses). Confirmed diagnosis for
Crohn’s disease or for other conditions informs the downstream treatment strategies and thus affect
subsequent health outcomes. Additional diagnostic value offered by capsule endoscopy is expected to
improve the effectiveness of downstream disease management via improved treatment selection.
A modelling technique is employed to quantitatively determine the additional health outcomes
associated with the use of capsule endoscopy when compared with no capsule endoscopy scenario
(i.e., treatment after CT, MRI and/or SBFT). This involves transforming health outcomes (i.e., better
targeted treatment selection via improved diagnosis) and their QoL implications to quality-adjusted
life years (QALYs).
A decision analytic model is employed. It is proposed that health states included in the model are
defined by two elements; true disease status (Crohn’s disease or other bowel disease) and capsule
endoscopy result (confirmed diagnosis of Crohn’s disease or other bowel conditions, or indeterminate
results).
Figure 2 depicts a proposed model structure as prepared by the applicant and Figure 3 presents an
updated and expanded view of the proposed decision tree. In line with the proposed listing, patients
enter the model with “suspected Crohn’s disease” after having already undergone colonoscopy with
ileoscopy and small bowel imaging (including CTE, MRE and/or SBFT). An additional model structure
with all the modelling steps fully outlined is presented in
For the ‘capsule endoscopy’ arm, the hypothetical cohort of patients is distributed into health states
depending on their true disease state and their capsule endoscopy results. Patients who receive an
indeterminate capsule endoscopy result are assumed to receive treatment for Crohn’s disease. For
the ‘no capsule endoscopy’ arm, all patients are assumed to receive treatment for Crohn’s disease,
while they may or may not in fact have Crohn’s disease.
For simplicity, the patient’s true disease status is assumed to be either Crohn’s disease or other bowel
disease. It is envisaged that, as per a similar cost-effectiveness study performed for CTE by Levesque
et al (2010), a certain bowel condition such as irritable bowel syndrome will be used as a proxy for
the costs and utilities for ‘other bowel disease’. It is acknowledged that other conditions can be
identified on capsule endoscopy, e.g., malignancy. It is however assumed that the magnitude and
nature of healthcare resource use and QoL implications of ‘other bowel disease’ are adequately
captured by those associated with irritable bowel syndrome.
21
Figure 2 Proposed structure of Markov model for the cost-effectiveness analysis of capsule endoscopy
Abbreviations: CTE, computed tomography enterography; MRE, magnetic resonance enterography; NPV, negative predictive value; OBD, other bowel disease; PPV, positive predictive value; QALY, quality
adjusted life year; SBFT; small bowel follow through; Tx, treatment
22
Figure 3 Expanded structure of a proposed model for the cost-effectiveness analysis of capsule endoscopy versus no capsule endoscopy
Abbreviations: CT, computed tomography; MRI, magnetic resonance imaging; SBFT; small bowel follow through; Tx, treatment
23
Cost inputs describing each of the health state would mainly account for the administered treatments.
While exact resource items are to be determined, for example, patients treated for Crohn’s disease
receive a mix of first-line therapies for the condition including 5-aminosalicylates (5-ASAs),
corticosteroids, azathioprine and 6-mercaptopurine. In addition, the costs of capsule endoscopy
would be added to the capsule endoscopy arm based on the proposed MBS benefit.
The utility values experienced by patients in each health state will be derived from the clinical
literature. Incremental QALYs for the capsule endoscopy arm would reflect that the treatment
selection would be more targeted, thus producing better effectiveness, when compared with the
comparator arm.
It is anticipated that the model includes a time horizon of one year; minimising uncertainty potentially
associated with long-term extrapolation. Once patients receive capsule endoscopy, patients remain in
their health states for the duration of the model.
24
References
Caunedo-Álvarez A., Romero-Vazquez J. and Herrerias-Gutierrez J.M. Patency and agile capsules
(2008) World J Gastroenterol 14(34):5269-5273.
Gearry, RB, Ajlouni, Y et al 2007. 5-Aminosalicylic acid (mesalazine) use in Crohn's disease: a survey
of the opinions and practice of Australian gastroenterologists, Inflammatory Bowel Diseases, 13 (8),
1009-1015.
Levesque BG, Cipriano LE, Chang SL, Lee KK, Owens DK, Garber AM. Cost effectiveness of alternative
imaging strategies for the diagnosis of small-bowel Crohn's disease. Clin Gastroenterol Hepatol. 2010
Mar;8(3):261-7
Li F, Gurudu SR, De PG, Sharma VK, Shiff AD, Heigh RI, Fleischer DE, Post J, Erickson P, Leighton
JA. Retention of the capsule endoscope: a single-center experience of 1000 capsule endoscopy
procedures. Gastrointest Endosc 2008;68:174-180.
Lichtenstein GR, Hanauer SB, Sandborn WJ; Practice Parameters Committee of American College of
Gastroenterology. Management of Crohn's disease in adults. Am J Gastroenterol. 2009
Feb;104(2):465-83.
Morrison, G, Headon, B et al 2009. Update in inflammatory bowel disease, Australian Family
Physician, 38 (12), 956-961.
Satsangi, J, Silverberg, MS et al 2006. The Montreal classification of inflammatory bowel disease:
Controversies, consensus, and implications, Gut, 55 (6), 749-753.
Sidhu, R, Sanders, DS et al 2008. Guidelines on small bowel enteroscopy and capsule endoscopy in
adults, Gut, 57 (1), 125-136.
Solem, CA, Loftus, J et al 2008. Small-bowel imaging in Crohn's disease: a prospective, blinded, 4way comparison trial, Gastrointestinal Endoscopy, 68 (2), 255-266.
Vanfleteren L, van der Schaar P, Goedhard J. Ileus related to wireless capsule retention in suspected
Crohn's disease: emergency surgery obviated by early pharmacological treatment. Endoscopy
2009;41 Suppl 2:E134-E135.
Vogel J, Moreira A, Baker M, et al. CT enterography for Crohn's disease: accurate preoperative
diagnostic imaging. Dis Colon Rectum. 2007;50:1761–1769.
Yamada, T. 2009. Textbook of gastroenterology, 5th edn. Chichester, West Sussex; Hoboken, NJ:
Blackwell.
25
Appendix: Applicant’s response to issues in the prior
assessment
Issues identified in the prior assessment
An earlier application requesting MBS listing of capsule endoscopy for the diagnosis of suspected
small bowel Crohn’s disease was lodged for consideration by MSAC in February 2010 and was
subsequently rejected. At the time, MSAC concluded that the available evidence for the safety,
effectiveness and cost-effectiveness of capsule endoscopy under the proposed indication was
inconclusive to support the listing; “there were substantial deficiencies with the evidence base around
comparative safety, accuracy and clinical effectiveness data for capsule endoscopy relative to
alternative ways of investigating patients with suspected small bowel Crohn disease ” (Public Summary
Document, PSD; MSAC 2011, pg13). Nonetheless, MSAC acknowledged a clear clinical need for
capsule endoscopy in the requested indication, and recognised that the requested population
constitutes a very small subgroup of patients who cannot be diagnosed through other means.
The re-submission will address key issues and data gaps identified in the earlier submission for
capsule endoscopy in the diagnosis of small bowel Crohn’s disease. Table 9 presents the key issues
raised in the previous MSAC submission, as well as the approaches used to address them. In
summary, the re-submission will better define the positioning of capsule endoscopy in the diagnosis
of small bowel Crohn’s disease and present comparative clinical evidence that is relevant to the redefined positioning (and thus patient population and comparator). Presentation of safety evidence, in
particular, the risk of capsule retention, is also expanded. A linked evidence approach (with modelled
economic evaluation) will be included to translate the available clinical evidence to final patient
outcomes (e.g., life years and/or quality-adjusted life years, QALYs) and allow its relative costeffectiveness to be adequately assessed by the MSAC.
26
Table 9: Key issues identified by MSAC in the Public Summary Document for the 2010 submission for capsule
endoscopy in the diagnosis of small bowel Crohn’s disease
Issue
Proposed changes to the approach of re-submission outlined in this
DAP
Clarification of diagnostic algorithm and
positioning of capsule endoscopy
“In the clinical flow chart, capsule endoscopy
is a replacement test for repeat radiology
(Computed Tomography (CT)/CT
enterography (CTE) or magnetic resonance
imaging (MRI)/ Magnetic Resonance
Enterography (MRE)) and a replacement for
treating the patient empirically based on a
suspicion of Crohn disease which could not
be confirmed (ie incremental to prior
testing).”
(Public Summary Document; MSAC 2011,
pg 4)
Applicability of clinical data
“…the assessment indicated that the
evidence is not relevant to the proposed
population in which it will be used, which is
the group of patients who are hardest to
diagnose and for which the applicant is
indicating capsule endoscopy would assist”.
(Public Summary Document; MSAC 2011,
pg 8).
Comparative diagnostic accuracy
“…the assessment report provided no basis
to conclude that the diagnostic accuracy of
capsule endoscopy was superior to the
alternative investigations of CT or MRI in
any population with suspected Crohn
disease.”
(Public Summary Document; MSAC 2011,
pg 8).
Linked evidence approach
“…the assessment did not identify any direct
studies comparing the health outcomes of
patient populations with suspected small
bowel Crohn’s disease assessed with and
without capsule endoscopy. ESC pointed to
the issue that evidence for accuracy, change
in management and the expected benefit of
changes in treatment on health outcomes
were all achieved using a linked evidence
approach” (Public Summary Document;
MSAC 2011, pg13).
It is proposed that capsule endoscopy should be reserved for patients who
were not able to achieve a confirmed positive or negative diagnosis for
Crohn’s disease through prior endoscopy and radiographic imaging.
Radiographic imaging may include magnetic resonance enterography
(MRE), computed tomography enterography (CTE) or small bowel follow
through (SBFT). Therefore, the evidence most relevant to this submission
consists of trials of capsule endoscopy versus empirical treatment.
As acknowledged by MSAC, this represents the patient sub-group that is
hardest to diagnose with the current diagnostic technologies (5% of the total
patient population with suspected Crohn’s disease).
This positioning of capsule endoscopy in the diagnosis of small bowel
Crohn’s disease has received KOL endorsement.
The evidence most relevant to this submission consists of trials of capsule
endoscopy versus empiric treatment. The literature review will search for
direct evidence for the impact of capsule endoscopy on health outcomes in
the appropriate population (i.e. patients with suspected Crohn’s disease who
were unable to be diagnosed with CTE, MRE or SBFT).
The main comparator for capsule endoscopy in the requested indication is
empiric treatment. Patients who receive capsule endoscopy will have
already undergone small bowel imaging with CTE, MRE or SBFT. Repeat
investigations using radiographic imaging do not improve the diagnostic
yield.
The literature review will search for direct evidence for the impact of capsule
endoscopy on health outcomes. In the absence of direct evidence, the resubmission will present indirect evidence indicating the impact of capsule
endoscopy on clinical management and patient outcomes. The use of a
linked evidence approach is not unusual when looking at the impact of a
diagnostic test on clinical outcomes. Studies that might be used in a linked
evidence approach include the following:
-
-
Diagnostic accuracy and diagnostic yield studies of capsule
endoscopy in the appropriate population (i.e. patients with
suspected Crohn’s disease who were unable to be diagnosed with
CTE, MRE or SBFT).
Studies reporting the impact of capsule endoscopy on patient
management.
Studies reporting health outcomes and costs
Ideally, these studies will provide comparative data with empiric treatment;
27
Issue
Proposed changes to the approach of re-submission outlined in this
DAP
however where necessary the search will also include non-comparative
studies, or studies including comparisons with other diagnostic modalities.
Decision analytic modeling may be employed in a linked evidence approach
by translating the available evidence into final patient outcomes (e.g., life
years or/and quality-adjusted life years, QALYs).
Safety of capsule endoscopy
“MSAC noted ESC advice that the evidence
for the safety of the intervention did not
address sufficiently the issue of retention of
the capsule”.
(Public Summary Document; MSAC 2011,
pg 8).
The resubmission will present several reasons for why the risk of capsule
retention was overstated in the previous assessment report, including the
following:
-
-
-
Technical failure
“MSAC noted that capsule endoscopy might
fail to provide a diagnostic result for
technical reasons which are unique to the
technology, such as battery failure before
transition through the small bowel, the visual
field being obscured due to mucus or
intestinal contents, and difficulty in
swallowing the 11 mm by 26 mm capsule”
(Public Summary Document; MSAC 2011,
pg 10).
Justifying cost-effectiveness
Due to a perceived lack of comparative
effectiveness data, the previous MSAC
assessment report did not perform a costeffectiveness analysis. The approach to the
economic evaluation was therefore a
presentation of the costs and possible
consequences of capsule endoscopy and
comparators. A healthcare system
perspective was used, which included the
cost to the government via the MBS and
cost to the patient.
Patients who are eligible for capsule endoscopy will have already
undergone CTE or MRE, both of which can be used to identify
strictures.
In patients who are suspected of having strictures, Pillcam® SB
comes with a dissolvable capsule (Agile™) to test the patency of
the gastrointestinal tract before capsule endoscopy. The
submission will present clinical evidence to demonstrate the
efficacy of the patency capsule in patients with suspected
strictures, leading to a reduced risk of harm.
The evidence pertaining to retention identified in the previous
MSAC assessment report will be updated and critiqued in the
context of the proposed indication
The clinical significance of retention will also be investigated.
In instances of technical failure, Given Imaging will provide an extra capsule,
free of charge under the standard warranty terms. If the Pillcam® SB is
unable to adequately visualise the small bowel for other reasons, this would
be picked up in studies of diagnostic accuracy and will be accounted for in
the economic evaluation.
The submission will present a cost-effectiveness analysis based on a
superiority claim (efficacy and/or safety).
It is envisaged that a modeled economic evaluation will be presented to
translate the diagnostic accuracy/effectiveness data into final patient
outcomes (e.g., life years or/and quality-adjusted life years, QALYs).
Consistent with the previous MSAC assessment report, a healthcare system
perspective will be used, including the cost to the government and cost to
the patient.
Abbreviations: CT, computed tomography; CTE, computed tomography enterography; DAP, decision analytic protocol; MBS,
Medicare Benefits Schedule; MRI, magnetic resonance imaging; MRE, magnetic resonance enterography; PSD, Public
Summary Document
28
In addition to the issues summarised in , the PSD also highlighted the following points which do not
require any additional changes to the approach of the re-submission:
1. MSAC agreed with ESC that the term “small bowel radiology” was ambiguous and implied that
CT and/or MRI be included as prerequisite tests rather than alternative tests. MSAC agreed
that, if capsule endoscopy were not definitive in its diagnosis of small bowel Crohn disease,
patients may still need to be considered for histological examination such as could be
obtained with balloon enteroscopy (BE) before being put on long-term drugs which are both
toxic and potentially expensive. However, MSAC agreed that, from a consumer’s perspective,
capsule endoscopy would be preferable to BE on the grounds of comfort and risk. The
clarification that CE is to be used after CTE or MRE removes this issue.
2. MSAC further agreed that the number of patients who would be eligible for the proposed
indication for capsule endoscopy would be very small. In most patients with isolated small
bowel Crohn’s disease, the disease affects that part of the small bowel which can usually be
visualised with terminal ileoscopy at the time of colonoscopy. The re-submission will include
updated budget impact calculations.
3. MSAC also agreed that any MBS listing of capsule endoscopy in small bowel Crohn’s disease
should not permit monitoring or surveillance of diagnosed patients. The requested item
restriction specifically excludes the monitoring or surveillance of diagnosed patients. In fact,
MSAC Application 1190 is reviewing the use of MRE for monitoring/surveillance of diagnosed
patients.
Safety
The major safety issue raised in the previous assessment report for capsule endoscopy was the
possibility of capsule retention. The primary basis for this concern was a single study that reported a
capsule retention rate of 15% in patients with suspected Crohn’s disease undergoing capsule
endoscopy (Ge et al., 2004). The re-submission will present several reasons for why this risk was
overstated in the previous assessment report, including the following:
1. Patients who are eligible for capsule endoscopy will have already undergone CTE or MRE,
both of which can be used to identify strictures with a relatively high success rate (Vogel et
al., 2007), at no additional cost.
2. In patients who are suspected of having strictures, Pillcam ® SB comes with a dissolvable
capsule (Agile™) to test the patency of the gastrointestinal tract before capsule endoscopy.
In an international multi-centre study, 106 patients with known strictures ingested the Agile™
patency capsule. The study found 56% of patients excreted the Agile™ capsule intact and
subsequently underwent complete capsule endoscopy. None of these patients subsequently
experienced retention after swallowing the Pillcam ® SB.
3. The evidence pertaining to retention identified in the previous MSAC assessment report will
be updated and critiqued in the context of the proposed indication.
29
4. The clinical significance of retention will also be investigated. For example, most retained
capsules are asymptomatic; in one retrospective study of 1000 capsule endoscopies with a
1.4% retention rate, none of the patients had any symptoms of capsule retention (Li et al.,
2008). Additionally, in the small number of cases where surgical intervention for capsule
recovery is required, they are frequently correctional in nature to address the underlying
cause of illness, thereby generating health outcomes in themselves.
Apart from the risk of retention, the previous MSAC Assessment Report for capsule endoscopy
concluded the procedure is safe with a low risk of adverse events. Furthermore, capsule endoscopy is
associated with no exposure to ionising radiation, like MRI/MRE (which is not currently reimbursed)
but unlike SBFT or CT/CTE.
These questions will be addressed and discussed at length in the re-submission.
30